Treatment of kidney clear cell carcinoma, lung adenocarcinoma and glioblastoma cell lines with hydrogels made of DNA nanostars

2022 ◽  
Author(s):  
Manuela Leo ◽  
Enrico Lattuada ◽  
Debora Caprara ◽  
Luisa Salvatori ◽  
Andrea Vecchione ◽  
...  

Overcoming the systemic administration of chemotherapy to reduce drug toxicity and the application of personalised medicine are two of the major challenges in the treatment of cancer. To this aim,...

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yu-Hsun Chang ◽  
Dah-Ching Ding

Abstract Background Cell lines are extremely useful for both basic and clinical research. Thus, establishing endometrial cancer cell lines with malignant histology is important. This study aimed to extensively characterize an endometrial clear cell carcinoma cell line. Methods This cell line, named 150,057, was derived from the endometrial clear cell cancer of a 63-year-old woman. The morphology, chromosomes, chemosensitivity, tumor markers, xenotransplantation characteristics, and cancer-related genes of the cell line were characterized. Results This cell line exhibited adequate growth, being passaged more than 70 times. The morphology of the cells was polygonal with a cobblestone-like appearance. Karyotyping of the cell line revealed a hypodiploid chromosomal number. 150057 cells expressed CA19–9 and CA125. The cell line was sensitive to doxorubicin, paclitaxel, carboplatin, and cisplatin. After the cells were transplanted into the subcutaneous region of non-obese diabetic-severe combined immunodeficiency mice, they generated xenograft tumors with similar histology as the original tumor. A total of 59 somatic nucleotide mutations were identified in 25 of the 53 examined tumor suppressor genes and oncogenes. Two novel mutations were found in FGFR3 and ARID1A. Conclusion We established and characterized an endometrial clear cell carcinoma cell line that may be useful in carcinogenesis and treatment research for endometrial cancer.


2014 ◽  
Vol 24 (5) ◽  
pp. 829-837 ◽  
Author(s):  
Mahiru Kawano ◽  
Seiji Mabuchi ◽  
Toshiko Kishimoto ◽  
Takeshi Hisamatsu ◽  
Yuri Matsumoto ◽  
...  

ObjectivesThe objective of this study was to investigate the chemotherapeutic agents that produce the strongest synergistic effects when combined with trabectedin against ovarian clear cell carcinoma (CCC), which is regarded as an aggressive chemoresistant histological subtype.MethodsUsing 4 human CCC cell lines (RMG1, RMG2, KOC7C, and HAC2), the cytotoxicities of trabectedin, SN-38, topotecan, doxorubicin, cisplatin, and paclitaxel as single agents were first assessed using the MTS assay. Then, the cytotoxicities of combination treatments involving trabectedin and 1 of the other 4 agents were evaluated by isobologram analysis to examine whether these combinations displayed synergistic, additive, or antagonistic effects. The antitumor activities of the combination treatments were also examined using cisplatin-resistant and paclitaxel-resistant CCC sublines, which were derived from the parental CCC cells by continuously exposing them to cisplatin or paclitaxel. Finally, we determined the effect of everolimus on the antitumor efficacy of trabectedin-based combination chemotherapy.ResultsConcurrent exposure to trabectedin and SN-38 or topotecan resulted in synergistic interactions in all 4 CCC cell lines. Among the tested combinations, trabectedin plus SN-38 was the most effective cytotoxic regimen. The combination of trabectedin plus SN-38 also had strong synergistic effects on both the cisplatin-resistant and paclitaxel-resistant CCC cell lines. Treatment with everolimus significantly enhanced the antitumor activity of trabectedin plus SN-38 or topotecan.ConclusionsCombination treatment with trabectedin and SN-38 displays the greatest cytotoxic effect against ovarian CCC. Our in vitro study provides the rationale for future clinical trials of trabectedin plus irinotecan with or without everolimus in patients with ovarian CCC in both the front-line chemotherapy setting and as a second-line treatment of recurrent CCC that had previously been treated with cisplatin or paclitaxel.


PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88587 ◽  
Author(s):  
Heejei Yoon ◽  
Yoon-La Choi ◽  
Ji-Young Song ◽  
Ingu Do ◽  
So Young Kang ◽  
...  

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 360-360 ◽  
Author(s):  
G. Gibney ◽  
P. Conrad ◽  
S. A. Aziz ◽  
R. L. Camp ◽  
B. E. Schwartz ◽  
...  

360 Background: c-Met is a receptor tyrosine kinase involved in normal cellular growth and vascular development. It has also been identified as a proto-oncogene. Activating c-Met mutations and indirect c-Met activation via von Hippel-Lindau gene silencing have been demonstrated in renal cell carcinoma (RCC) for papillary and clear cell histologic subtypes, respectively. We studied c-Met expression in a large cohort of RCC tumors and investigated in vitro activity of the new selective c-Met inhibitor, ARQ 197. Methods: Tissue microarrays were performed to analyze c-Met protein expression in situ in 317 RCC tumor specimens using Automated Quantitative Analysis (AQUA). Western blots were performed for c-Met, phospho-c-Met and downstream pathway markers in 6 RCC cell lines (A498, ACHN, Caki-1, Caki-2, 769P, and 786-O). In vitro activity of ARQ 197 was studied by cell viability and clonogenic assays, and by changes in c-Met and down-stream mediators. Results: c-Met expression is higher in RCC than adjacent normal renal tissue (p < 0.0001) and is expressed in all subtypes of RCC, including clear cell carcinoma; expression is highest in papillary and sarcomatoid subtypes. Greater c-Met expression correlates with higher tumor grade (p = 0.0019) and clinical stage (p = 0.0208), and is an independent predictor of poor overall survival (Multivariate Cox LR 5.7, p = 0.017). c-Met expression correlates to decreased survival in the clear cell subset as well. c-Met protein is activated (phosphorylated) in all 6 RCC cells. ARQ 197 inhibits cell growth in RCC cell lines at nanomolar concentrations (IC50 350-680 nM) and inhibits colony formation at 500 nM. ARQ 197 decreases phosphorylation of c-Met in time- and dose-dependent patterns with dose-dependent decreases in phospho-ERK. Conclusions: c-Met expression is an independent predictor of survival in RCC, including clear cell subtype, suggesting that it is a potential therapeutic target worthy of further investigation. ARQ 197 effectively inhibits proliferation of clear cell carcinoma cell lines. Further preclinical studies are planned to determine mechanism of cellular arrest and apoptosis and markers of drug sensitivity and resistance. [Table: see text]


2021 ◽  
Vol 11 (4) ◽  
pp. 263
Author(s):  
Hyo Jae Shin ◽  
Kyung Jin Lee ◽  
Minchan Gil

Cereblon (CRBN) is a component of the E3 ubiquitin ligase complex that plays crucial roles in various cellular processes. However, no systematic studies on the expression and functions of CRBN in solid tumors have been conducted to date. Here, we analyzed CRBN expression and its clinical value using several bioinformatic databases. CRBN mRNA expression was downregulated in various cancer types compared to normal cells. Survival analysis demonstrated that overall survival was significantly positively correlated with CRBN expression in some cancer types including lung adenocarcinoma (LUAD), kidney renal clear cell carcinoma (KIRC), and skin cutaneous melanoma (SKCM). CRBN expression was downregulated regardless of clinicopathological characteristics in LUAD and KIRC. Analysis of genes that are commonly correlated with CRBN expression among KIRC, LUAD, and SKCM samples elucidated the potential CRBN-associated mechanisms of cancer progression. Overall, this study revealed the prognostic value of CRBN and its potential associated mechanisms, which may facilitate the development of anti-cancer therapeutic agents.


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